Early treatment for tuberculosis in sepsis patients in Sub-Saharan Africa

A Randomized Clinical Trial of Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa

This study is testing whether starting tuberculosis treatment right away can help reduce death rates in sepsis patients with HIV in Uganda and Tanzania.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 436 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Virginia (Academic / other)
• Locations: 2 sites (Sanya Juu and 1 other locations)
• Trial ID: NCT04618198 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of immediate anti-tuberculosis (TB) therapy in patients with sepsis in Uganda and Tanzania, particularly those living with HIV. It employs a randomized 2x2 factorial design to compare empiric immediate initiation of anti-TB therapy plus standard care against diagnosis-dependent therapy, as well as sepsis-specific dosing versus conventional weight-based dosing. The primary goal is to determine if these approaches can reduce 28-day mortality rates among patients presenting with sepsis. Secondary objectives include assessing in-hospital and 6-month mortality rates.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older living with HIV who are admitted to the hospital with signs of infection and meet specific clinical criteria.

Not a fit: Patients with known active TB or those currently receiving anti-TB therapy will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce mortality rates in sepsis patients with undiagnosed TB in Sub-Saharan Africa.

How similar studies have performed: While the approach is novel in this specific context, similar studies have shown promise in improving outcomes for sepsis patients with underlying infections.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female aged ≥18 years living with HIV
4. Admitted to hospital with 1) clinical concern for infection; 2) ≥2 qSOFA score criteria (Glasgow Coma Scale score \<15, a respiratory rate ≥22, or a systolic blood pressure ≤90 mmHg or a mean arterial pressure of ≤65 mmHg)
5. Resident within a pre-defined geographic area to ensure TB clinic follow-up
6. For females of reproductive potential: use of highly effective contraception through 28 days

Exclusion Criteria:

1. Known active TB or receiving anti-TB therapy
2. Pregnancy or lactation. Women will undergo urine pregnancy screening. Pregnant women will be excluded due to the possible toxicity and teratogenicity of high dose rifampin and isoniazid included in anti-TB therapy as well as possible teratogenicity of dolutegravir which is recommended as first-line antiretroviral therapy in this study.
3. Known allergic reactions to the components of the anti-TB therapy
4. Treatment with another investigational drug or other intervention within one month
5. Known liver disease
6. Alcohol use \> 14 standardized drinks per week and/or \> 4 drinks per day for men and \>7 standardized drinks per week and/or \>3 drinks per day for women, defined as 14 grams of ethanol, as found in example 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80 proof spirits
7. Positive serum cryptococcal antigen test
8. Current treatment with a drug known to have significant interaction with anti-TB therapy

Where this trial is running

Sanya Juu and 1 other locations

• Kibong'oto Infectious Diseases Hospital — Sanya Juu, Tanzania (Recruiting)
• Mbarara University Science Technology — Mbarara, Uganda (Recruiting)

Study contacts

• Principal investigator: Christopher Moore, MD — University of Virginia
• Study coordinator: Christopher Moore, MD

Conditions Tuberculosis; HIV I Infection; Sepsis